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Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT04614103
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : August 2, 2021
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE October 21, 2020
First Posted Date  ICMJE November 3, 2020
Last Update Posted Date August 2, 2021
Actual Study Start Date  ICMJE May 7, 2021
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
Objective Response Rate [ Time Frame: Up to 60 months ]
To evaluate the efficacy of LN-145 in patients with metastatic NSCLC without an actionable driver mutation who have disease progression on or following a single line of approved systemic therapy consisting of combined immune checkpoint inhibitor(s) (CPI[s]) + chemotherapy ± bevacizumab, as determined by objective response rate (ORR), using the RECIST v1.1, as assessed by the Independent Review Committee (IRC) (Cohorts 1 and 2) or by the Investigator (Cohorts 3 and 4)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
  • Objective Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Objective Response Rate (ORR) per RECIST v1.1
  • Complete Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
  • Duration of Response [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
  • Disease Control Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
  • Progression-Free Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
  • Overall Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Overall Survival (OS)
  • Adverse Events [ Time Frame: Up to 60 months ]
    To characterize the safety profile of LN-145 in NSCLC patients, as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)
  • Core Biopsies [ Time Frame: Up to 60 months ]
    For Cohort 3 only: To evaluate the efficiency of generating LN-145 from tumor core biopsies; Percentage successful TIL products generated from core biopsies
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer
Official Title  ICMJE A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer
Brief Summary This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic NSCLC.
Detailed Description LN-145 is a ready-to-infuse, autologous TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving an NMA lymphocyte depleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Non Small Cell Lung Cancer
Intervention  ICMJE
  • Biological: LN-145
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
    Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes
  • Biological: LN-145
    A tumor sample is harvested via core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
    Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes
Study Arms  ICMJE
  • Experimental: Cohort 1
    Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1) (tumor proportion score [TPS] < 1%) prior to their CPI treatment.
    Intervention: Biological: LN-145
  • Experimental: Cohort 2
    Patients whose tumors expressed PD-L1 (TPS ≥ 1%) prior to their CPI treatment.
    Intervention: Biological: LN-145
  • Experimental: Cohort 3

    Patients whose tumors do not express PD-L1 (TPS < 1%) prior to their CPI treatment and who are unable to safely undergo a surgical harvest for TIL generation due to at least one of the following:

    • Unacceptable surgical risk
    • Surgically approachable lesion is required for Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 assessment
    Intervention: Biological: LN-145
  • Experimental: Cohort 4
    Patients who have been previously treated with LN-145 in Cohort 1, 2, or 3 of this study.
    Intervention: Biological: LN-145
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 28, 2020)
95
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2026
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed histologic diagnosis of Non-Small-Cell Lung Carcinoma confirmation.
  • Have received a single line of systemic therapy that included CPI and chemotherapy with documented radiographic disease progression on or following this single line of systemic therapy.
  • LVEF > 45%, NYHA Class 1; cardiac stress test required
  • FEV1>50% or FEV1/FVC>0.7 (6 min walk test if unable to perform or unreliable spirometry).
  • At least 1 resectable lesion.
  • Previously irradiated lesion must have radiographic progression prior to harvest.
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an estimated life expectancy of ≥ 6 months
  • Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and for 12 months after receiving all protocol-related therapy.

Exclusion Criteria:

  • Patients who have known oncogene driver mutations (eg, EGFR, ALK, ROS) which are sensitive to targeted therapies.
  • Patients who have symptomatic and/or untreated brain metastases.
  • Patients who have organ allograft or prior cell transfer within the past 20 years.
  • Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or other steroid equivalent. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent may be eligible.
  • Patients who have any form of primary immunodeficiency
  • Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
  • Patients who have had another primary malignancy within the previous 3 years
  • Participation in another interventional clinical study within 21 days of the initiation of treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04614103
Other Study ID Numbers  ICMJE IOV-LUN-202
2020-003629-45 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Iovance Biotherapeutics, Inc.
Study Sponsor  ICMJE Iovance Biotherapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Iovance Biotherapeutics Study Team Iovance Biotherapeutics
PRS Account Iovance Biotherapeutics, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP